The present invention relates to compact electrochemical sensor systems, methods for plug-and-play assembly of compact electrochemical sensor systems, and methods for field testing for metals.
Because of the toxicity of environmental contaminants, a reliable analytical system is desired for monitoring them in complex environmental matrices. For metal species, such assays are usually carried out in central laboratories using ICP-AES or ICP-MS. However, in view of the huge labor and analytical costs or time delays associated with centralized laboratory analyses there are immediate needs for developing portable analytical systems for on-site monitoring. Development of a portable system for analysis of environmental contaminants will greatly improve the quality and efficiency for on-site characterization of chemical contamination and will allow real-time monitoring of exposure to toxic metals.
Microfabrication technology has been utilized to integrate whole laboratory systems onto microchips. These systems have been termed microscale total analytical systems1 (xcexc-TAS), and their development has become an active research area. Numerous xcexc-TAS systems have been developed and reported in the literature, and have shown very promising capabilities1-7. The advantages of the xcexc-TAS approach include the ability to analyze extremely small volume samples, increased speed of analysis, reduction in reagent consumption, and consequent reduction in waste disposal.
Most fabrication processes for microfluidic chemical and biological systems involve photolithography and the associated wet etching processes to form the microchannels, valves, and interconnects. Historically, silicon and glasses have been the most widely used materials 1-4. Most devices constructed from these materials are planar, which makes it difficult to incorporate a number of functions into the microfluidic component and to efficiently direct fluid flow to the required site.
Analyte detection remains an important issue for microchip devices. Most analyses have been conducted using large detectors, such as laser-induced fluorescence3-4 and mass spectrometry5-8. In some applications, electrochemical detection can be sensitive, compact and integrated into a small size9-10.
Biological monitoring is recognized as a critically important approach for accurately estimating absorbed doses of chemicals from all potential exposure routes. However, the application of biomonitoring is hampered by numerous factors including, the need for complicated and/or expensive analytical methods, difficulty in obtaining needed biological specimens and the lack of understanding of the pharmacokinetic properties of a chemical, all of which are needed to accurately estimate internal dose.
To facilitate the use of biomonitoring, there is a need to develop reliable, portable and cost-effective analytical instruments for on-site monitoring of chemicals, employing a relevant biological matrix readily obtainable from workers.
1. A. Manz, J. C. Fettinger, E. Verpoorte, H. Lundi, H. M. Widmer, and D. J. Harrison, xe2x80x9cMicromachining of monocrystaline silicon and glass for chemical analysis systems: a look into next century""s technology or just a fashionable craze?xe2x80x9d Trends in Anal. Chem., 10, 144, 1991
2. G. T. A. Kovacs, K. Petersen, M. Albin, xe2x80x9cSilicon micromachining: sensors to systems,xe2x80x9d Anal. Chem.; 68, pp407A-412A, 1996
3. L. C. Waters, S. C. Jacobson, N. Kroutchinina, J. Khandurina, R. S. Foote, J. M. Ramsey, xe2x80x9cMultiple sample PCR amplification and electrophoretic analysis on a microchip,xe2x80x9d Anal. Chem. 70, pp. 5172-5176, 1998
4. G. Ocvirk, T. Tang, D. J. Harrison, xe2x80x9cOptimization of confocal epifluorescence microscopy for microchip-based miniaturized total analysis systems,xe2x80x9d Analyst, 123, pp. 1429-1434, 1998
5. Y. Lin, N. Xu, D. W. Matson, R. D. Smith, xe2x80x9cMicrofabricated dual-microdialysis and capillary isoelectric focusing devices for cleanup and separation/mass spectrometric analysis of biomolecules,xe2x80x9d in the Micro Total Analysis Systems""98; Ed.: Harrison, D. J. and den Berg, A. V.; pp3343-346; Kluwer Academic Publishers, Boston, 1998
6. N. Xu, Lin, Y., S. A. Hofstadler, D. W. Matson, C. J. Call, R. D. Smith, xe2x80x9cA microfabricated dialysis device for sample cleanup in electrospray ionization mass spectrometry,xe2x80x9d Anal. Chem. 70, pp. 3553-3556, 1998
7. F. Xiang, Y. Lin, J. Wen, D. W. Matson, R. D. Smith, xe2x80x9cAn integrated microfabricated device for dual dialysis and ESI coupled to ion trap mass spectometry for rapid analysis of complex biological samples,xe2x80x9d Anal. Chem., 71 pp1485-1490, 1999
8. Q. Xue, F. Foret, Y. M. Dunayevskiy, P. M. Zavracky, N. E. McGruer, B. L. Karger, xe2x80x9cMultichannel microchip electrospray mass spectrometry,xe2x80x9d Anal. Chem., 69, pp. 426-430, 1997
9. C. Belmont, M. L. Tercier, J. Buffle, G. C. Fiaccabrino, Koudelka-Hep, xe2x80x9cMercury-plated iridium-based microelectrode array for trace metals detection by voltammetry: optimum conditions and reliability,xe2x80x9d Anal. Chim. Acta, 329, pp203-214, 1996
10. S. P. Kounaves, W. Deng, P. R. Hallock, G. T. A. Kovacs, C. W. Storment, xe2x80x9cIridium-based ultramicroelectrode array fabricated by microlithography,xe2x80x9d Anal. Chem., 66, pp418-423, 1994
11. C. E. Bohs, M. C. Linhares, P. T. Kissinger, Current Separations, 13, pp6-8, 1994
12. F. Zhou, J. T. Aronson, M. W. Ruegnitz, xe2x80x9cHigh-throughput fast-scan anodic stripping voltanmmetry in a microflow system,xe2x80x9d Anal. Chem., 69, pp728-733, 1997
The present invention provides a compact, integrated electrochemical sensor system having at least three components: a pump, a mixing layer, and an electrochemical cell. The mixing layer has a mixing channel having at least one inlet and at least one outlet. A via (preferably a tube) connects an outlet of the mixing channel with an inlet to the electrochemical cell. The device can be described in terms of layers to indicate the compactness of the device and because a layer configuration can be easily assembled and transported. In preferred embodiments, various components, for example reservoirs, pumps, mixing layers and electrochemical cells, can be readily attached or detached from the device. This method of attaching components is referred to as xe2x80x9cplug-and-playxe2x80x9d in which various components can be plugged into (or unplugged from) the device without needing to use adhesive, clamping or other cumbersome means to attach the components. In another preferred aspect, the mixing layer has separate channels: one for liquid transport from a reservoir, and a mixing channelxe2x80x94this novel configuration allows very space efficient packing of components and is compatible with the plug-and-play concept.
The invention also includes methods measuring metals in fluids by running samples through a compact, integrated electrochemical sensor. In preferred embodiments, the inventive methods are used for field testing for metals in blood or saliva.
The invention described herein can use a significantly different design and fabrication approach, as compared with conventional lab-on-a-chip technology. In the present invention, functional laminates arranged in a stacked architecture. Each laminate layer performs a specific function, such as fluid reservoirs, mixing chamber, or a reaction chamber. Microsensors, micropumps, and valves can easily be integrated into such a laminated structure.
Various designs of the invention can provide numerous advantages such as portability, ease of cleaning, and the ability to substitute, add or remove parts. Furthermore, the inventive sensors can be microfabricated at relatively low cost. The invention can also provide a low-cost and rapid method for on-site and in situ determination of toxic metals in environmental water and for non-invasive monitoring for occupational exposure to metals such as lead.
The subject matter of the present invention is particularly pointed out and distinctly claimed in the concluding portion of this specification. However, both the organization and method of operation, together with further advantages and objects thereof, may best be understood by reference to the following description taken in connection with accompanying drawings wherein like reference characters refer to like elements.